The fact that many human diseases develop at the level of cells is well established. Rudolph Virchow's “Cellular Pathology” (Virchow Rudolph, Cellular Pathology, Berlin, 1858) has become a leading principle of pathology. While the localization of the initiation of these diseases—the cell—was thereby defined, the variety of mechanisms that cause a cell to malfunction have remained insufficiently understood.
One of these pathological mechanisms that have remained obscure is a deficiency or a lack of bioenergy in the cell. Under physiological conditions the bioenergy of a cell is provided from sugar, proteins and fats that is catabolyzed in the cell. The common pathways of catabolism of food and for the generation of bioenergy in form of ATP are the Tricarboxylic Acid Cycle or Citric Acid Cycle (Krebs cycle) and subsequent cellular energy pathway, the cellular Respiratory Chain (respiratory chain) as well as the closely connected Urea Cycle (urea cycle).
The possibility of a deficiency of one or more of the Krebs cycle, respiratory chain and the urea cycle compounds are further enhanced by the fact that these biochemical pathways involve a multitude of enzymatic steps. Just recently the first molecular diseases involving an enzyme deficiency of the Krebs cycle have been characterized (Bourgeron T., et al., J. Clin. Invest. 93:2514, 1994; Rustin et al., Biochim Biophys Acta 1361:185,1997; Patel, M. S. and Harris R. A. FASEB J 9:1164,1995; Shoffner, J. M. and Wallace D. C. in C. R. Scriver et al. (Eds.) The Metabolic and Molecular Bases of Inherited Disease, 7th ed. New York: McGraw-Hill, 1995, p. 1535). Genetic disorders for one or more of these enzymes and/or one or more of the coenzymes involved inevitably lead to a deficiency of one or more of the biochemical compounds of these pathways.
Recently, several coenzymes (e.g. thiamine, nicotinic acid, ascorbic acid, riboflavin, Mg++) of the Krebs cycle have been used in the prevention and adjunct treatment of certain health conditions (Beyond deficiency, 2nd Symposium of the New York Academy of Sciences on Vitamins, New York 1992; E. Ziegler, L. J. Filer (eds.) Present Knowledge in Nutrition 7th edition. ILSI Press, Washington D.C. 1996; Matthias Rath, Alexandra Niedzwiecki. J Appl. Nutrition 48: 68–78, 1996). However, the biochemical compounds of the Krebs cycle itself, the respiratory chain and the closely connected urea cycle have not similarly been used.
Therefore there is a need for methods and compositions to prevent and treat malfunctioning of bioenergy metabolism of cells.